Project Summary/Abstract Imaging plays a critical role in the diagnosis, staging, and follow-up of neuroblastoma (NB). Radiolabeled metaiodobenzylguanidine (MIBG) is extensively used for imaging NB and is recommended for staging and follow-up of NB. In this early-phase study, we are evaluating a novel radiotracer, meta-fluorobenzylguanidine, or 18F-MFBG. We hypothesize that imaging with this positron-labeled analog of MIBG will provide a more convenient single-day imaging alternative using superior scanning technology (PET/CT or PET/MR) and enhanced quantitative assessment of disease in these NB patients. Imaging with 123I-MIBG is limited in several respects, including: a) inferior image quality related to the physical properties of the isotope that limit the dose of tracer that can be administered and the technology of the gamma camera and single photon imaging (SPECT), which has lower resolution than PET imaging; b) need for an imaging agent that not only targets lesions but also provides a superior high-contrast image to assess organs such as lung and liver; c) less optimal modality (SPECT imaging) due to limited ability to quantify uptake or measure metabolic activity of disease; and d) inconvenient two-day imaging process that requires injection on Day 1, followed by imaging on Day 2 to allow for optimal uptake of the tracer by the tumor and clearance of background activity [best target-to-background (T/BG) ratio]. An imaging modality that is more convenient and allows for superior quantification of disease is critically needed. PET imaging is superior to SPECT (higher resolution and ability to quantify lesion uptake and metabolic activity), and 18F-MFBG is a fluoride-labeled analog of MIBG with targeting properties similar to MIBG. The positron emitter 18F allows for imaging with a PET scanner and can provide high-contrast images with high T/BG ratios within one to three hours post-injection, a significantly more convenient option for patients than waiting 24 hours and returning to the clinic. The lesion uptake and distribution can be quantified with 18F-MFBG PET imaging. Additionally, imaging with 18F-MFBG will allow for combined PET/MR imaging, thereby reducing the radiation dose through the elimination of the CT component of PET/CT and its associated ionizing radiation. We hypothesize that PET imaging with 18F-MFBG will be safe and feasible and will target NB lesions comparable to or better than 123I-MIBG. Due to a convenient one-day imaging schema and PET imaging with PET/CT or PET/MR, this novel radiotracer is expected to play a critical role and replace 123I-MIBG for imaging of NB in the future. This is a Phase I/IIa study for early assessment of this novel imaging agent. Results of this study will be used to plan larger Phase II studies and, if successful, Phase III studies for validation of results and with the ultimate goal of achieving FDA approval.